Alterations of colonic function in the Winnie mouse model of spontaneous chronic colitis
In this study, we investigated in vivo intestinal transit in radiographic studies and in vitro motility of the isolated colon in organ bath experiments. We compared neuromuscular transmission using conventional intracellular recording between distal colon of Winnie and C57BL/6 mice and smooth muscle contractions using force displacement transducers. Chronic inflammation in Winnie mice was confirmed by detection of lipocalin-2 in fecal samples over 4 wk and gross morphological damage to the colon. Colonic transit was faster in Winnie mice. Motility was altered including decreased frequency and increased speed of colonic mig...
Source: AJP: Gastrointestinal and Liver Physiology - January 10, 2017 Category: Gastroenterology Authors: Robinson, A. M., Rahman, A. A., Carbone, S. E., Randall-Demllo, S., Filippone, R., Bornstein, J. C., Eri, R., Nurgali, K. Tags: RESEARCH ARTICLE Source Type: research

Expression of Cav1.3 calcium channel in the human and mouse colon: posttranscriptional inhibition by IFN{gamma}
It has been hypothesized that apically expressed L-type Ca2+ channel Cav1.3 (encoded by CACNA1D gene) contributes toward an alternative TRPV6-independent route of intestinal epithelial Ca2+ absorption, especially during digestion when high luminal concentration of Ca2+ and other nutrients limit TRPV6 contribution. We and others have implicated altered expression and activity of key mediators of intestinal and renal Ca2+ (re)absorption as contributors to negative systemic Ca2+ balance and bone loss in intestinal inflammation. Here, we investigated the effects of experimental colitis and related inflammatory mediators on col...
Source: AJP: Gastrointestinal and Liver Physiology - January 10, 2017 Category: Gastroenterology Authors: Radhakrishnan, V. M., Gilpatrick, M. M., Parsa, N. A., Kiela, P. R., Ghishan, F. K. Tags: RESEARCH ARTICLE Source Type: research

Maturity and age influence chief cell ability to transdifferentiate into metaplasia
The plasticity of gastric chief cells is exemplified by their ability to transdifferentiate into spasmolytic polypeptide-expressing metaplasia (SPEM) after parietal cell loss. We sought to determine if chief cell maturity is a limiting factor in the capacity to transdifferentiate. Mist1–/– mice, previously shown to form only immature chief cells, were treated with DMP-777 or L635 to study the capability of these immature chief cells to transdifferentiate into a proliferative metaplastic lineage after acute parietal cell loss. Mist1–/– mice treated with DMP-777 showed fewer chief cell to SPEM transit...
Source: AJP: Gastrointestinal and Liver Physiology - January 10, 2017 Category: Gastroenterology Authors: Weis, V. G., Petersen, C. P., Weis, J. A., Meyer, A. R., Choi, E., Mills, J. C., Goldenring, J. R. Tags: RESEARCH ARTICLE Source Type: research

Ca2+/calmodulin/MLCK pathway initiates, and RhoA/ROCK maintains, the internal anal sphincter smooth muscle tone
(Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - January 10, 2017 Category: Gastroenterology Authors: Rattan, S. Tags: PERSPECTIVES Source Type: research

Irritable bowel syndrome: a gut microbiota-related disorder?
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal (GI) disorders. Despite its prevalence, the pathophysiology of IBS is not well understood although multiple peripheral and central factors are implicated. Recent studies suggest a role for alterations in gut microbiota in IBS. Significant advances in next-generation sequencing technology and bioinformatics and the declining cost have now allowed us to better investigate the role of gut microbiota in IBS. In the following review, we propose gut microbiota as a unifying factor in the pathophysiology of IBS. We first describe how gut microbiota can be i...
Source: AJP: Gastrointestinal and Liver Physiology - January 10, 2017 Category: Gastroenterology Authors: Bhattarai, Y., Muniz Pedrogo, D. A., Kashyap, P. C. Tags: REVIEW Source Type: research

Novel insights into fecal incontinence in men
Fecal incontinence (FI) in men is common, yet data on sex differences in clinical features, physiology, and treatment are scarce. Our aim was to provide insights into FI in males compared with females. Prospectively collected data from 73 men and 596 women with FI in a tertiary referral center were analyzed. Anorectal physiology, clinical characteristics, and outcome of instrumented biofeedback (BF) were recorded. Thirty-one men with FI proceeded to BF and were matched with 62 age-matched women with FI who underwent BF. Men with FI had higher resting, squeeze, and cough anal sphincter pressures (P < 0.001) and were more...
Source: AJP: Gastrointestinal and Liver Physiology - December 31, 2016 Category: Gastroenterology Authors: Mazor, Y., Jones, M., Andrews, A., Kellow, J. E., Malcolm, A. Tags: RESEARCH ARTICLE Source Type: research

Probiotic mixture VSL#3 reduces colonic inflammation and improves intestinal barrier function in Muc2 mucin-deficient mice
In this study we used Muc2 mucin-deficient (Muc2–/–) and Muc2+/+ littermates to test whether the probiotic mixture VSL#3 requires an intact mucin barrier to exert its beneficial effect. VSL#3 alone reduced basal colonic proinflammatory cytokine levels and improved epithelial barrier function in Muc2–/– animals. Similarly, in dextran sulfate sodium-induced colitis, VSL#3 dampened the proinflammatory chemokines KC, monocyte chemoattractant protein-1, and macrophage inflammatory protein-2 and upregulated the tissue regeneration growth factors transforming growth factor-β, fibroblast growth factor-...
Source: AJP: Gastrointestinal and Liver Physiology - December 31, 2016 Category: Gastroenterology Authors: Kumar, M., Kissoon-Singh, V., Coria, A. L., Moreau, F., Chadee, K. Tags: RESEARCH ARTICLE Source Type: research

Regulation and function of bone morphogenetic protein signaling in colonic injury and inflammation
In this study we report a series of novel observations that underscore the importance of bone morphogenetic protein (BMP) signaling in the regulation of colonic homeostasis during the development of injury and inflammation. In particular, we present evidence that BMP signaling mitigates the response of the colonic epithelium to injury and inflammation and that cytokines, such as TNF-α and IL-1β, inhibit the expression of BMP-4. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - December 31, 2016 Category: Gastroenterology Authors: Ji, T., Takabayashi, H., Mao, M., Han, X., Xue, X., Brazil, J. C., Eaton, K. A., Shah, Y. M., Todisco, A. Tags: RESEARCH ARTICLE Source Type: research

Weight gain in mice on a high caloric diet and chronically treated with omeprazole depends on sex and genetic background
We examined what factors, e.g., diet composition, microbiota, genetic strain, and sex, might affect weight gain in mice fed a high caloric diet while on OM. Inbred C57BL/6J strain, a 50:50 hybrid (B6SJLF1/J) strain, and mice on a highly mixed genetic background were fed four diets: standard chow (STD, 6% fat), STD with 200 ppm OM (STD + O), a high-energy chow (HiE, 11% fat), and HiE chow with OM (HiE + O) for 17 wk. Metabolic analysis, body composition, and fecal microbiota composition were analyzed in C57BL/6J mice. Oral glucose tolerance tests were performed using mice on the mixed background. After 8 wk, female and male...
Source: AJP: Gastrointestinal and Liver Physiology - December 31, 2016 Category: Gastroenterology Authors: Saqui-Salces, M., Tsao, A. C., Gillilland, M. G., Merchant, J. L. Tags: RESEARCH ARTICLE Source Type: research

A model of the enteric neural circuitry underlying the generation of rhythmic motor patterns in the colon: the role of serotonin
We discuss the role of multiple cell types involved in rhythmic motor patterns in the large intestine that include tonic inhibition of the muscle layers interrupted by rhythmic colonic migrating motor complexes (CMMCs) and secretomotor activity. We propose a model that assumes these motor patterns are dependent on myenteric descending 5-hydroxytryptamine (5-HT, serotonin) interneurons. Asynchronous firing in 5-HT neurons excite inhibitory motor neurons (IMNs) to generate tonic inhibition occurring between CMMCs. IMNs release mainly nitric oxide (NO) to inhibit the muscle, intrinsic primary afferent neurons (IPANs), glial c...
Source: AJP: Gastrointestinal and Liver Physiology - December 31, 2016 Category: Gastroenterology Authors: Smith, T. K., Koh, S. D. Tags: REVIEW ARTICLE Source Type: research

Relationship between gastric motility and liquid mixing in the stomach
The relationship between gastric motility and the mixing of liquid food in the stomach was investigated with a numerical analysis. Three parameters of gastric motility were considered: the propagation velocity, frequency, and terminal acceleration of peristaltic contractions. We simulated gastric flow with an anatomically realistic geometric model of the stomach, considering free surface flow and moving boundaries. When a peristaltic contraction approaches the pylorus, retropulsive flow is generated in the antrum. Flow separation then occurs behind the contraction. The extent of flow separation depends on the Reynolds numb...
Source: AJP: Gastrointestinal and Liver Physiology - December 12, 2016 Category: Gastroenterology Authors: Miyagawa, T., Imai, Y., Ishida, S., Ishikawa, T. Tags: NEUROGASTROENTEROLOGY AND MOTILITY Source Type: research

Glycine prevents metabolic steatohepatitis in diabetic KK-Ay mice through modulation of hepatic innate immunity
Strategies for prevention and treatment of nonalcoholic steatohepatitis remain to be established. We evaluated the effect of glycine on metabolic steatohepatitis in genetically obese, diabetic KK-Ay mice. Male KK-Ay mice were fed a diet containing 5% glycine for 4 wk, and liver pathology was evaluated. Hepatic mRNA levels for lipid-regulating molecules, cytokines/chemokines, and macrophage M1/M2 markers were determined by real-time RT-PCR. Hepatic expression of natural killer (NK) T cells was analyzed by flow cytometry. Body weight gain was significantly blunted and development of hepatic steatosis and inflammatory infiltr...
Source: AJP: Gastrointestinal and Liver Physiology - December 12, 2016 Category: Gastroenterology Authors: Takashima, S., Ikejima, K., Arai, K., Yokokawa, J., Kon, K., Yamashina, S., Watanabe, S. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Catalpol restores LPS-elicited rat microcirculation disorder by regulation of a network of signaling involving inhibition of TLR-4 and SRC
LPS-induced microvascular hyperpermeability and hemorrhage play a key role in the development of sepsis, the attenuation of which might be an important strategy to prevent sepsis. However, the current clinical therapies have proven to be inefficient in improving the prognosis for patients with sepsis. Catalpol, an iridoid glycoside extracted from the roots of Rehmannia, has been reported to protect against LPS-induced acute lung injury through a Toll-like receptor-4 (TLR-4)-mediated NF-B signaling pathway. However, it is still unknown whether catalpol can be an effective treatment to ameliorate the LPS-induced microvascula...
Source: AJP: Gastrointestinal and Liver Physiology - December 12, 2016 Category: Gastroenterology Authors: Zhang, Y.-P., Pan, C.-S., Yan, L., Liu, Y.-Y., Hu, B.-H., Chang, X., Li, Q., Huang, D.-D., Sun, H.-Y., Fu, G., Sun, K., Fan, J.-Y., Han, J.-Y. Tags: INFLAMMATION, IMMUNITY, FIBROSIS, AND INFECTION Source Type: research

Hydroxylases regulate intestinal fibrosis through the suppression of ERK-mediated TGF-{beta}1 signaling
Fibrosis is a complication of chronic inflammatory disorders such as inflammatory bowel disease, a condition which has limited therapeutic options and often requires surgical intervention. Pharmacologic inhibition of oxygen-sensing prolyl hydroxylases, which confer oxygen sensitivity upon the hypoxia-inducible factor pathway, has recently been shown to have therapeutic potential in colitis, although the mechanisms involved remain unclear. Here, we investigated the impact of hydroxylase inhibition on inflammation-driven fibrosis in a murine colitis model. Mice exposed to dextran sodium sulfate, followed by a period of recov...
Source: AJP: Gastrointestinal and Liver Physiology - December 12, 2016 Category: Gastroenterology Authors: Manresa, M. C., Tambuwala, M. M., Radhakrishnan, P., Harnoss, J. M., Brown, E., Cavadas, M. A., Keogh, C. E., Cheong, A., Barrett, K. E., Cummins, E. P., Schneider, M., Taylor, C. T. Tags: TRANSLATIONAL HUMAN PATHOPHYSIOLOGY Source Type: research

Advanced spatiotemporal mapping methods give new insights into the coordination of contractile activity in the stomach of the rat
We used spatiotemporal mapping of strain rate to determine the direction of propagation and amplitudes of the longitudinal and circumferential components of antrocorporal (AC) contractions and fundal contractions in the rat stomach maintained ex vivo and containing a volume of fluid that was within its normal functional capacity. In the region of the greater curvature the longitudinal and circular components of AC contractions propagated synchronously at right angles to the arciform geometric axis of the stomach. However, the configuration of AC contractions was U shaped, neither the circular nor the longitudinal component...
Source: AJP: Gastrointestinal and Liver Physiology - December 12, 2016 Category: Gastroenterology Authors: Lentle, R. G., Reynolds, G. W., Hulls, C. M., Chambers, J. P. Tags: NEUROGASTROENTEROLOGY AND MOTILITY Source Type: research